Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance.
Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance.
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DOI：
10.1016/j.celrep.2017.06.039
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发表时间：
2017-07-05
期刊：
影响因子：
8.8
通讯作者：
Gauguier D
中科院分区：
文献类型：
--
作者：
Dumas ME;Rothwell AR;Hoyles L;Aranias T;Chilloux J;Calderari S;Noll EM;Péan N;Boulangé CL;Blancher C;Barton RH;Gu Q;Fearnside JF;Deshayes C;Hue C;Scott J;Nicholson JK;Gauguier D
肠道微生物组对代谢和行为特征的影响被广泛接受，尽管微生物组衍生的代谢物所涉及的尚不清楚。我们在等基因C57BL/6J小鼠群体（n = 50）中进行了基于非靶向尿液1H-NMR谱的代谢表型分析，结果表明微生物-宿主共代谢产物是前驱（即早期）标记物，预测代谢（肥胖和葡萄糖稳态）和行为（焦虑和活动）结果的未来差异，准确率为94%-100%。其中一些代谢物也调节疾病表型，最好的例子是三甲胺- n -氧化物（TMAO），这是微生物-宿主共同代谢的产物，可预测未来的肥胖、糖耐量受损（IGT）和行为，同时减少内质网应激和3T3-L1脂肪细胞的脂肪生成。慢性体内TMAO治疗通过增加胰岛素分泌来限制hfd喂养小鼠和离体胰岛的IGT。我们强调了微生物代谢物的前驱潜力，以预测疾病结果及其在塑造哺乳动物表型异质性方面的潜力。包括甲胺在内的微生物代谢物可预测表型异质性TMAO可减轻内质网应激并减少脂肪细胞中的脂肪生成TMAO可改善体内胰岛素分泌并恢复葡萄糖耐量Dumas等人在等基因小鼠种群模型中研究了高脂肪饮食干预引起的代谢和行为表型异质性。使用1H-NMR波谱，他们识别介入前尿液代谢特征（包括微生物-宿主共代谢物），预测未来的表型异质性。特别是，氧化三甲胺纠正内质网应激和葡萄糖耐量。
The influence of the gut microbiome on metabolic and behavioral traits is widely accepted, though the microbiome-derived metabolites involved remain unclear. We carried out untargeted urine 1H-NMR spectroscopy-based metabolic phenotyping in an isogenic C57BL/6J mouse population (n = 50) and show that microbial-host co-metabolites are prodromal (i.e., early) markers predicting future divergence in metabolic (obesity and glucose homeostasis) and behavioral (anxiety and activity) outcomes with 94%–100% accuracy. Some of these metabolites also modulate disease phenotypes, best illustrated by trimethylamine-N-oxide (TMAO), a product of microbial-host co-metabolism predicting future obesity, impaired glucose tolerance (IGT), and behavior while reducing endoplasmic reticulum stress and lipogenesis in 3T3-L1 adipocytes. Chronic in vivo TMAO treatment limits IGT in HFD-fed mice and isolated pancreatic islets by increasing insulin secretion. We highlight the prodromal potential of microbial metabolites to predict disease outcomes and their potential in shaping mammalian phenotypic heterogeneity. High-fat diet drives phenotypic heterogeneity in metabolism and behavior Microbial metabolites, including methylamines, predict phenotypic heterogeneity TMAO attenuates ER stress and reduces lipogenesis in adipocytes TMAO improves insulin secretion and restores glucose tolerance in vivo Dumas et al. study the metabolic and behavioral phenotypic heterogeneity induced by a high-fat diet intervention in an isogenic mouse population model. Using 1H-NMR spectroscopy, they identify pre-interventional urinary metabolic signatures (including microbial-host co-metabolites) predicting future phenotypic heterogeneity. In particular, TMAO corrects endoplasmic reticulum stress and glucose tolerance.
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影响因子：
7.7
作者：
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通讯作者：
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DOI：
10.1152/ajpendo.00332.2001
发表时间：
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